Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(4):e2022156 1 Subcutaneous Granuloma Annulare in an Atypical Age Group in Immediate Post-Covid-19 Phase Lovleen Kaur1, Disha Chakraborty1, Surabhi Dayal2, Sunita Singh3, Karamvir Yadav4 1 Department of Dermatology, Venereology and Leprology, Pt. B.D. Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India 2 Department of Dermatology, Venereology and Leprology, Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana, India 3 Department of Pathology, Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana, India 4 Department of Medicine, Pt. B.D. Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India Key words: Granuloma Annulare, Covid-19, SARS-Cov-2, Palisading granuloma, Subcutaneous GA Citation: Kaur L, Chakraborty D, Dayal S, Singh S, Yadav K. Subcutaneous Granuloma Annulare in an Atypical Age Group in Immediate Post-Covid-19 Phase. Dermatol Pract Concept. 2022;12(4):e2022156. DOI: https://doi.org/10.5826/dpc.1204a156 Accepted: January 7, 2022; Published: October 2022 Copyright: ©2022 Kaur et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Lovleen Kaur, MD, Senior Resident, Department of Dermatology, Venereology and Leprology, Pt. B.D. Sharma Post Graduate Institute of Medical Sciences, Rohtak, Haryana, India. Email: dr.lovleen555@gmail.com Introduction Granuloma Annulare (GA) is a benign, self-limiting, chronic granulomatous disorder. Viruses are one of the triggering factors. Only two case reports of SARS-Cov-2 triggered GA are reported till date; one- in an adult (localized GA) and another localized, generalized and subcutaneous GA (SCGA) in pediatric patients [1,2]. SCGA is rare in adults, especially geriatric population. Case Presentation A 63-year-old male presented with abrupt onset, multiple, asymptomatic, skin-colored to erythematous nodules involv- ing abdomen, bilateral upper and lower limbs for 7 days. Lesions progressed rapidly without systemic complaints ex- cept for malaise. Patient denied insect bite/ trauma before the onset. There was no ulceration/ discharge from the nodules. Twenty days earlier, he had fever, sore-throat, mal- aise, body-aches and anosmia (Positive Rapid Antigen test for SARS-Cov-2). Patient received symptomatic treatment (Paracetamol and Etoricoxib) under home-isolation. SARS- Cov-2 infection was also present in wife and daughter. Clinically, there were 23 discrete, subcutaneous nodules, firm to hard, non-tender, non-fluctuant, mobile, symmetri- cally distributed predominantly over extensors of bilateral thighs and few on legs, upper-arms and abdomen. Majority were appreciated on palpation only while few lesions had erythematous hue. The largest lesion measured 4  x  3  cm2 over right upper thigh whereas others varied from 1 x 1 to 1.5 x 2 cm2 (Figure 1). Routine biochemistry, hemogram, anti- streptolysin O titres, and Mantoux test were normal. C-reactive protein and ESR were high. SARS-Cov-2 IgG titre was 64 AU/mL(positive). Serology for HBV, HCV, 2 Research Letter | Dermatol Pract Concept. 2022;12(4):e2022156 HIV, Parvovirus-B19, HSV-1 and 2, EBV, CMV, Adenovi- rus, Mycoplasma pneumoniae, ricketssiosis were negative. Considering the age, he was investigated for any associated malignancy. CECT-Chest revealed subtle ground glass opac- ities in bilateral upper lobes and fibro-atelectatic bands in apical zones suggesting post-covid sequelae. CECT-Abdomen and pelvis were normal. Deep incisional skin biopsy consid- ering differential diagnosis of Erythema Nodosum (EN), Subcutaneous Sweet Syndrome and SCGA was performed. Histopathology was consistent with SCGA (Figure 2). Alcian Blue staining was also positive for mucin. Intralesional tri- amcinolone acetonide (10mg/ml) was injected in divided sittings after informed consent from the patient resulting in complete remission within fifteen days. Conclusions SCGA commonly affects trauma-prone sites like extensors of distal extremities. In our case it involved proximal upper and lower extremities, and abdomen. Possibility of drugs incit- ing SCGA is unlikely as patient had taken Paracetamol and Etoricoxib in past without any dermatological complaints. The conspicuous absence of lesional pain, tenderness, er- ythema and concomitant systemic features ruled out EN and Sweet syndrome. Absence of vasculitis on histopathol- ogy eliminates causes of ‘septal panniculitis with vasculitis’. Histopathologically, positive Alcian blue stain for mucin excludes differential of Miescher Radial Granuloma of EN. Although, rheumatoid nodules are also asymptomatic and Figure 1. (A) Marked subcutaneous nodules on bilateral thighs which were better appreciated on palpa- tion only (red arrow depicts biopsy site). (B) Faintly erythematous nodules on medial aspect of left thigh and lower leg (black arrows). Figure 2. (A) Normal epidermis, perivascular lympho-histiocytic infiltrate in the dermis (blue arrow) and palisading of histiocytes in subcutaneous fat (red arrow) on H&E, 40x. (B) Interstitial infiltrate of lym- phocytes and histiocytes with focal palisading and mucinous degeneration in subcutaneous fat marked by red arrow (H&E, 100x). Research Letter | Dermatol Pract Concept. 2022;12(4):e2022156 3 simulates SCGA on histopathology, the former has more fibrin deposition than mucin causing ‘red’ granulomas unlike ‘blue’ granulomas in SCGA. SARS-Cov-2 induces cytokine storm, producing IL-1β, IL-6, TNF-α, IL-12/23 which may precipitate SCGA as a re- active phenomenon. Vascular damage associated with viruses causing immune-complex deposition may also explain chronic granulomatous changes seen in GA. To conclude, geriatric SCGA may be another dermatological manifesta- tion triggered by SARS-Cov-2. It may enforce a huge diag- nostic dilemma in the elderly confusing it with cutaneous metastasis necessitating meticulous diagnostic workup. References 1. García-Gil MF, Monte Serrano J, García García M, Matovelle Ochoa C, Ara-Martín M. Granuloma annulare triggered by SARS- CoV-2 infection. The first reported case. J Dermatol. 2021;48(1):e1- e2. DOI:10.1111/1346-8138.15594. PMID: 331 69426. 2. Mazzotta F, Troccoli T, Bonifazi E. Granuloma annulare and SARS-CoV-2 pandemic. Eur J Pediat Dermatol. 2020;30(2):83-87. DOI: 10.26326/2281-9649.30.2.2105.